1. Field of the Invention
The present invention relates to novel imidazole alkaloid compounds that have been isolated as a form of chloride salt from a root extract of Lepidium meyenii Walp, with the common name Maca, and identified as 1,3-bis(phenylmethyl)-4,5-dimethyl-1H-imidazlium chloride and 1,3-bis(phenylmethyl)-2,4,5-trimethyl-1H-imidazlium chloride. More specifically, this invention further relates to the use of these novel compounds to treat proliferative diseases, such as but not limited to cancer.
2. Description of the State of Art
Lepidium meyenii (commonly referred to as Maca) is indigenous to the Andean Mountains at an altitude of higher than 10,000 feet. To the Andean Indians, Maca is a valuable commodity. Because so little else grows in the region, Maca is often traded with communities at lower elevations for other staples like rice, corn, and beans. The dried roots can be stored for up to seven years. Native Peruvians have traditionally utilized Maca since before the time of the Incas for both nutritional and medicinal purposes. Maca is an important staple in the diets of the people indigenous to the region since it has the highest nutritional value of any food crop grown there. The nutritional value of dried Maca root is high, resembling cereal grains such as maize, rice and wheat. It has 59% carbohydrates, 10.2% protein, 8.5% fiber and 2.2% lipids. It has a large amount of essential amino acids and higher levels of iron and calcium than potatoes. Maca contains important amounts of fatty acids including linolenic, palmitic and oleic acids. It is rich in sterols and has a high mineral content as well. In addition to its rich supply of essential nutrients, Maca contains alkaloids, tannins and saponins. It is rich in sugars, protein, starches, and essential minerals, especially iodine and iron. The tuber is consumed fresh or dried. The fresh roots are considered a treat and are baked or roasted in ashes much like sweet potatoes. The dried roots are stored and later boiled in water or milk to make a porridge. In addition, they are often made into a popular sweet, fragrant, fermented drink called maca chicha.
Maca has been used medicinally for centuries to enhance fertility in humans and animals. Soon after the Spanish conquest in South America, the Spanish found that their livestock were reproducing poorly in the highlands. The local Indians recommended feeding the animals Maca and so remarkable were the results that Spanish chroniclers gave in-depth reports. Even colonial records of some 200 years ago indicate that payments of roughly 9 tons of Maca were demanded from one Andean area alone for this purpose. Its fertility enhancing properties were supported clinically as early as 1961, when researchers discovered it increased the fertility of rats.
Maca is growing in world popularity due to its energizing effects, fertility enhancement and aphrodisiac qualities. Other traditional uses include increasing energy, stamina and endurance in athletes, promoting mental clarity, treating male impotence, and helping with menstrual irregularities and female hormonal imbalances including menopause and chronic fatigue syndrome. It is used as an alternative to anabolic steroids by bodybuilders due to its richness in sterols. Today, dried Maca roots are ground to powder and sold in drug stores in capsules as a medicine and food supplement to increase stamina and fertility. In Peruvian herbal medicine, Maca is also used as an immunostimulant, for anemia, tuberculosis, menstrual disorders, menopause symptoms, stomach cancer, sterility and other reproductive and sexual disorders as well as to enhance memory.
The cultivation of Maca is increasing in the highlands of the Andes to meet the growing demand world wide for medicinal uses. In this severely economically depressed region, the market created for Maca will offer new and important sources of income for the Indigenous Peoples of the Andes. A new cultivar of Maca has been identified in the major growing regions of the highlands, which will supply much of this new demand, and it has been named Lepidium peruvianum Chacon sp.
Aguila Calderon, M.D., the former dean of the Faculty of Human Medicine at the National University of Federico Villarreal in Lima uses maca for male impotence, erectile dysfunction, menopausal symptoms and general fatigue, and claims good results. Arizona physician Gary F. Gordon, M.D., former president of the American College for Advancement in Medicine, is also a maca supporter. He calls it “nature's Viagra”. The supposed mechanism of action is by normalizing steroid hormones such as testosterone, progesterone and estrogen. It acts on men to restore them to a healthy functional status in which they experience a more active libido. Maca may boost desire but does not share Viagra's erection-enhancing properties.
Scientist Gustavo Gonzales of Peru's Cayetano Heredia University, who led what the scientists say is the world's first study into maca's effect on humans, told a news conference the three-month trial involving 12 volunteer men pointed to an 180-200% lift in libido and up to a doubling of sperm production. Maca produced an increase in sex drive within two weeks. The study, funded by Peruvian pharmaceuticals company Hersil, also found maca reduced blood pressure and had no adverse effect on the heart. Although it also appeared to boost the production and movement of sperm, Gonzales said more research was needed as the test had been restricted to a very small sample.
To be consistent with Peruvian usage levels one should take 3,000-5,000 mg per day of maca, but one can certainly take more. The more maca or maca extract that is consumed, the more the likely benefit. Toxicity studies conducted on maca in the U.S. showed absolutely no toxicity or adverse pharmacological effects. In animal studies, the more maca animals consume, the stronger and more sexually active they become.
In 1981, Johns reported the presence of benzyl isothiocyanates and p-methoxybenzyl isothiocyanate in the roots, which have reputed aphrodisiac properties. Johns, T., J. Ethnobiol., 1:208-212 (1981). Dini, A., et al., also identified many fatty acids, amino acids, and sterols from the roots and tubers in 1994. Dini, A., et al., O. Food Chem. Toxicol., 49:347-349 (1994). A previous in vivo study on lipidic extracts conducted at PureWorld showed the enhancement of sexual function of the mice and rats. Zheng, B. L., et al., Urology, 55:598-602 (2000). Two classes of compounds, macaene and macamide, have been identified from the purified standardized products (MacaPure-01 and MacaPure-02), as well as minor constituents of sterols and isothiocyanates. Zheng, B. L., et al., Urology, 55:598-602 (2000); and Zheng, B. L., et al., Patent (pending), 1999.
There is still a need, therefore, for a process and procedure for isolating and purifying imidazole alkaloids from imidazole alkaloids containing biomass in a commercially viable manner that directly provides a high concentration of the various imidazole alkaloids that can be subsequently recovered in high yield and purity. There is a further need to determine whether any of the naturally occurring compounds have other beneficial therapeutic uses.